More than 50 percent of asthmatics have a body mass index (BMI) of greater than 30, and the majority of these patients have severe asthma that doesn’t respond well to traditional medication. Trying to determine why this happens has earned Anne Dixon, M.A., B.M., B.Ch., director of pulmonary disease and critical care medicine at The Robert Larner, M.D. College of Medicine at The University of Vermont, not one but two RO1 grants from the National Institutes of Health, with combined funding of $6.2 million.
Only 14 to 15 percent of NIH RO1 applications receive funding.
For one of the two studies, Dixon and colleagues, including co-principal investigator and Professor of Medicine Jason Bates, Ph.D., D.Sc., are working in conjunction with bariatric surgeons at the UVM Medical Center. Their team has pioneered the discovery that there are two types of asthma in this patient population: non-allergic late-onset asthma, which improves significantly after bariatric surgery; and allergic asthma, which saw improvement in symptoms after surgery, but no change in airway “twitchiness.”
To support the gathering of preliminary data necessary for the NIH proposals, Dixon and colleagues received both a UVM Medical Group research grant and a Department of Medicine grant. Each study – and the corresponding NIH grants – looked at one of these two asthma types.
Dixon, Bates and Ryan Walsh, M.D., assistant professor of radiology, propose that non-allergic late-onset asthma causes airways to collapse more easily than airways in lean patients, a phenomenon that medication doesn’t address, and that back pressure could be applied to help patients breathe. Currently, steroids are the traditional treatment for alleviating symptoms in this group of patients, many of whom end up on oral steroids, which causes additional weight gain and exacerbates the problem. This research team also includes Jeffrey Klein, M.D., Bradley Soule and John P. Tampas Green and Gold professor of radiology and David Kaminsky, M.D., professor of medicine in the Division of Pulmonary Disease and Critical Care Medicine.
The second study addresses allergic asthma, which looks quite different from the non-allergic variety, particularly in heavier patients. Dixon and Matthew Poynter, Ph.D., professor of medicine and her co-principle investigator on the study, will try to understand why early onset allergic (EOA) asthma tends to be more severe in patients who suffer from obesity, as well as develop therapies targeted specifically to these patients. The research team is looking at whether cells secreted from visceral adipose tissue found in the abdomens of obese allergic asthmatics affect the mitrochondrial function of airway epithelial cells in a way that leads to severe disease. Using materials collected from subjects enrolled in a longitudinal study of EOA asthmatics undergoing bariatric surgery, and novel mouse models, they will be exploring how obesity may alter airway cellular function, and how this results in disease. They’ll also be looking at the mechanisms by which weight loss may help obese patients – who often do not respond to available treatments – regain normal function.
The team will work with Wasef Abu-Jaish, MD, associate professor, and Patrick Forgione, M.D., associate professor of surgery, to follow patients with allergic asthma going through bariatric surgery.
(Erin Post, senior writer in the Larner College of Medicine’s Office of Medical Communications, contributed to this article.)